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Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value

Importance Although increasingly strong evidence suggests a role of maternal total cholesterol and low-density lipoprotein cholesterol (LDLC) levels during pregnancy as a risk factor for atherosclerotic disease in the offspring, the underlying mechanisms need to be clarified for future clinical applications. Objective To test whether epigenetic signatures characterize early fetal atherogenesis associated with maternal hypercholesterolemia and to provide a quantitative estimate of the contribution of maternal cholesterol level to fetal lesion size. Design, Setting, and Participants This autopsy study analyzed 78 human fetal aorta autopsy samples from the Division of Human Pathology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy. Maternal levels of total cholesterol, LDLC, high-density lipoprotein cholesterol (HDLC), triglycerides, and glucose and body mass index (BMI) were determined during hospitalization owing to spontaneous fetal death. Data were collected and immediately processed and analyzed to prevent degradation from January 1, 2011, through November 30, 2016. Main Outcomes and Measurements Results of DNA methylation and messenger RNA levels of the following genes involved in cholesterol metabolism were assessed: superoxide dismutase 2 ( SOD2 ), low-density lipoprotein receptor ( LDLR ), sterol regulatory element binding protein 2 (SREBP2) , liver X receptor α ( LXRα ), and adenosine triphosphate–binding cassette transporter 1 ( ABCA1 ). Results Among the 78 fetal samples included in the analysis (59% male; mean [SD] fetal age, 25 [3] weeks), maternal cholesterol level explained a significant proportion of the fetal aortic lesion variance in multivariate analysis (61%; P = .001) independently by the effect of levels of HDLC, triglycerides, and glucose and BMI. Moreover, maternal total cholesterol and LDLC levels were positively associated with methylation of SREBP2 in fetal aortas (Pearson correlation, 0.488 and 0.503, respectively), whereas in univariate analysis, they were inversely correlated with SREBP2 messenger RNA levels in fetal aortas (Pearson correlation, −0.534 and −0.671, respectively). Epivariations of genes controlling cholesterol metabolism in cholesterol-treated human aortic endothelial cells were also observed. Conclusions and Relevance The present study provides a stringent quantitative estimate of the magnitude of the association of maternal cholesterol levels during pregnancy with fetal aortic lesions and reveals the epigenetic response of fetal aortic SREBP2 to maternal cholesterol level. The role of maternal cholesterol level during pregnancy and epigenetic signature in offspring in cardiovascular primary prevention warrants further long-term causal relationship studies.

Many of the devastating pandemics and outbreaks of last centuries have been caused by enveloped viruses. The recent pandemic of Coronavirus disease 2019 (COVID-19) has seriously endangered the global health system. In particular, hospitals have had to deal with a frequency in the emergency room and a request for beds for infectious diseases never faced in the last decades. It is well-known that hospitals are environments with a high infectious risk. Environmental control of indoor air and surfaces becomes an important means of limiting the spread of SARS-CoV-2. In particular, to preserve an adequate indoor microbiological quality, an important non-pharmacological strategy is represented by Heating, Ventilation and Air Conditioning (HVAC) systems and finishing materials. Starting from the SARS-CoV-2 transmission routes, the paper investigates the hospital risk analysis and management, the indoor air quality and determination of microbial load, surface management and strategies in cleaning activities, HVAC systems' management and filters' efficiency. In conclusion, the paper suggests some strategies of interventions and best practices to be taken into considerations for the next steps in design and management.

High-resolution imaging is the gold standard to measure the functional and biological features of bone lesions. Imaging markers have allowed the characterization both of tumour heterogeneity and metabolic data. Besides, ongoing studies are evaluating a combined use of 'imaging markers', such as SUVs, MATV, TLG, ADC from PET and MRI techniques respectively, and several 'biomarkers' spanning from chemokine immune-modulators, such as PD-1, RANK/RANKL, CXCR4/CXCL12 to transcription factors, such as TP53, RB1, MDM2, RUNX family, EZH2, YY1, MAD2. Osteoimmunology may improve diagnosis and prognosis leading to precision medicine in bone lesion treatment. Areas covered: We investigated modalities (molecular and imaging approach) useful to identify bone lesions deriving both from primary bone tumours and from osteotropic tumours, which have a higher incidence, prevalence and prognosis. Here, we summarized the recent advances in imaging techniques and osteoimmunology biomarkers which could play a pivotal role in personalized treatment. Expert commentary: Although imaging and molecular integration could allow both early diagnosis and stratification of cancer prognosis, large scale clinical trials will be necessary to translate pilot studies in the current clinical setting.ADC: apparent diffusion coefficient; ALCAM: Activated Leukocyte Cell Adhesion Molecule; ALP: Alkaline phosphatases; BC: Breast cancer; BSAP: B-Cell Lineage Specific Activator; BSAP: bone-specific alkaline phosphatase; BSP: bone sialoprotein; CRIP1: cysteine-rich intestinal protein 1; CD44: cluster of differentiation 44; CT: computed tomography; CXCL12: C-X-C motif ligand 12; CXCR4: C-X-C C-X-C chemokine receptor type 4; CTLA-4: Cytotoxic T-lymphocyte antigen 4; CTX-1: C-terminal end of the telopeptide of type I collagen; DC: dendritic cell; DWI: Diffusion-weighted MR image; EMT: mesenchymal transition; ET-1: endothelin-1; FDA: Food and Drug Administration; FDG

Although hospital hygiene has a long history in Italy it is necessary to reflect about it because of the innovation in healthcare systems and because of the evolution due to European Union related activities. Different traditions exist in European countries about hospital hygiene and European Centre for Disease Prevention and Control (ECDC) adopted the term of "infection control and hospital hygiene" which includes all the engaged European healthcare professionals. We propose to modify hospital hygiene as "healthcare organisation hygiene" in order to focalise the attention to all care settings not only hospitals and to adopt the following definition: "all activities aimed to guarantee, in an appropriate, scientifically sound and efficient way, that structures and processes support healthcare practices in a safe comfortable and healthy environment both for patients, caregivers and healthcare workers". Hospital hygiene and its professionals, besides the long tradition, still remain a relevant pillar in guaranteeing quality and safety of healthcare in Italy.

Heatwaves represent a threat to human health and excess mortality is one of the associated negative effects. A health-based definition for heatwaves is therefore relevant, especially for early warning purposes, and it is here investigated via the Universal Thermal Climate Index (UTCI). The UTCI is a bioclimate index elaborated via an advanced model of human thermo-regulation that estimates the thermal stress induced by air temperature, wind speed, moisture and radiation on the human physiology. Using France as a testbed, the UTCI was computed from meteorological reanalysis data to assess the thermal stress conditions associated to heat-attributable excess mortality in five cities. UTCI values at different climatological percentiles were defined and evaluated in their ability to identify periods of excess mortality (PEMs) over 24 years. Using verification metrics such as the probability of detection (POD), the false alarm ratio (FAR) and the frequency bias (FB), daily minimum and maximum heat stress levels equal or above corresponding UTCI 95th percentiles (15±2°C and 34.5±1.5°C, respectively) for 3 consecutive days are demonstrated to correlate to PEMs with the highest sensitivity and specificity (0.69 ≤ POD ≤ 1, 0.19 ≤ FAR ≤ 0.46, 1 ≤ FB ≤ 1.48) than minimum, maximum and mean heat stress level singularly and other bioclimatological percentiles. This finding confirms the detrimental effect of prolonged, unusually high heat stress at day and night time and suggests the UTCI 95th percentile as a health meaningful threshold for a potential heat health watch warning system.